Pattern of integration in piggyBac-derived products administered to patients. (A) Distribution of total unique integration sites in 5 individual CARTELL trial (patients 1-3, 7, and 8) and 3 compassionate access (patients 4-6) products showing a similar insertion pattern in the product of patient 2 (within genes, 63%; exons, 5%; introns, 62%; promoters, 18%; cytosine guanine dinucleotide [CpG] islands, 1%; intergenic regions, 37%; and oncogenes, 9%) compared with the mean of other products (within genes, 65%; exons, 4%; introns, 61%; promoters, 15%; CpG islands, 1%; intergenic regions, 35%; and oncogenes, 7%). All products were from healthy stem cell transplant donors. (B) Distribution of CAR gene insertions in CAR T-cell products and published data sets (denoted with an asterisk in the image) for lentivirus, piggyBac, and retrovirus³⁷ compared with a statistically random distribution throughout the genome. The departure from an expected random distribution is indicated by the colored tile, with red denoting enrichment compared with random and blue indicating depleted compared with random. Note: Products administered to patients subsequently developing CAR T-cell malignancies (2 and 8) are highlighted in red lettering. The COSMIC database was accessed at https://cancer.sanger.ac.uk/cosmic/download.